Overlapping effects of neuropsychiatric symptoms and circadian rhythm on effort-based decision-making

Reviewer #1 (Public Review):

Summary:

This study uses an online cognitive task to assess how reward and effort are integrated in a motivated decision-making task. In particular the authors were looking to explore how neuropsychiatric symptoms, in particular apathy and anhedonia, and circadian rhythms affect behavior in this task. Amongst many results, they found that choice bias (the degree to which integrated reward and effort affects decisions) is reduced in individuals with greater neuropsychiatric symptoms, and late chronotypes (being an 'evening person').

Strengths:

The authors recruited participants to perform the cognitive task both in and out of sync with their chronotypes, allowing for the important insight that individuals with late chronotypes show a more reduced choice bias when tested in the morning.
Overall, this is a well-designed and controlled online experimental study. The modelling approach is robust, with care being taken to both perform and explain to the readers the various tests used to ensure the models allow the authors to sufficiently test their hypotheses.

Weaknesses:

This study was not designed to test the interactions of neuropsychiatric symptoms and chronotypes on decision making, and thus can only make preliminary suggestions regarding how symptoms, chronotypes and time-of-assessment interact.

Reviewer #2 (Public Review):

Summary:

The study combines computational modeling of choice behavior with an economic, effort-based decision-making task to assess how willingness to exert physical effort for a reward varies as a function of individual differences in apathy and anhedonia, or depression, as well as chronotype. They find an overall reduction in effort selection that scales with apathy and anhedonia and depression. They also find that later chronotypes are less likely to choose effort than earlier chronotypes and, interestingly, an interaction whereby later chronotypes are especially unwilling to exert effort in the morning versus the evening.

Strengths:

This study uses state-of-the-art tools for model fitting and validation and regression methods which rule out multicollinearity among symptom measures and Bayesian methods which estimate effects and uncertainty about those estimates. The replication of results across two different kinds of samples is another strength. Finally, the study provides new information about the effects not only of chronotype but also chronotype by timepoint interactions which are previously unknown in the subfield of effort-based decision-making.

Weaknesses:

The study has few weaknesses. One potential concern is that the range of models which were tested was narrow, and other models might have been considered. For example, the Authors might have also tried to fit models with an overall inverse temperature parameter to capture decision noise. One reason for doing so is that some variance in the bias parameter might be attributed to noise, which was not modeled here. Another concern is that the manuscripts discuss effort-based choice as a transdiagnostic feature - and there is evidence in other studies that effort deficits are a transdiagnostic feature of multiple disorders. However, because the present study does not investigate multiple diagnostic categories, it doesn't provide evidence for transdiagnosticity, per se.

Reviewer #3 (Public Review):

Summary:

In this manuscript, Mehrhof and Nord study a large dataset of participants collected online (n=958 after exclusions) who performed a simple effort-based choice task. They report that the level of effort and reward influence choices in a way that is expected from prior work. They then relate choice preferences to neuropsychiatric syndromes and, in a smaller sample (n<200), to people's circadian preferences, i.e., whether they are a morning-preferring or evening-preferring chronotype. They find relationships between the choice bias (a model parameter capturing the likelihood to accept effort-reward challenges, like an intercept) and anhedonia and apathy, as well as chronotype. People with higher anhedonia and apathy and an evening chronotype are less likely to accept challenges (more negative choice bias). People with an evening chronotype are also more reward sensitive and more likely to accept challenges in the evening, compared to the morning.

Strengths:

This is an interesting and well-written manuscript which replicates some known results and introduces a new consideration related to potential chronotype relationships which have not been explored before. It uses a large sample size and includes analyses related to transdiagnostic as well as diagnostic criteria. I have some suggestions for improvements.

Weaknesses:

(1) The novel findings in this manuscript are those pertaining to transdiagnostic and circadian phenotypes. The authors report two separate but "overlapping" effects: individuals high on anhedonia/apathy are less willing to accept offers in the task, and similarly, individuals tested off their chronotype are less willing to accept offers in the task. The authors claim that the latter has implications for studying the former. In other words, because individuals high on anhedonia/apathy predominantly have a late chronotype (but might be tested early in the day), they might accept less offers, which could spuriously look like a link between anhedonia/apathy and choices but might in fact be an effect of the interaction between chronotype and time-of-testing. The authors therefore argue that chronotype needs to be accounted for when studying links between depression and effort tasks.
The authors argue that, if X is associated with Y and Z is associated with Y, X and Z might confound each other. That is possible, but not necessarily true. It would need to be tested explicitly by having X (anhedonia/apathy) and Z (chronotype) in the same regression model. Does the effect of anhedonia/apathy on choices disappear when accounting for chronotype (and time-of-testing)? Similarly, when adding the interaction between anhedonia/apathy, chronotype, and time-of-testing, within the subsample of people tested off their chronotype, is there a residual effect of anhedonia/apathy on choices or not?
If the effect of anhedonia/apathy disappeared (or got weaker) while accounting for chronotype, this result would suggest that chronotype mediates the effect of anhedonia/apathy on effort choices. However, I am not sure it renders the direct effect of anhedonia/apathy on choices entirely spurious. Late chronotype might be a feature (induced by other symptoms) of depression (such as fatigue and insomnia), and the association between anhedonia/apathy and effort choices might be a true and meaningful one. For example, if the effect of anhedonia/apathy on effort choices was mediated by altered connectivity of the dorsal ACC, we would not say that ACC connectivity renders the link between depression and effort choices "spurious", but we would speak of a mechanism that explains this effect. The authors should discuss in a more nuanced way what a significant mediation by the chronotype/time-of-testing congruency means for interpreting effects of depression in computational psychiatry.

(2) It seems that all key results relate to the choice bias in the model (as opposed to reward or effort sensitivity). It would therefore be helpful to understand what fundamental process the choice bias is really capturing in this task. This is not discussed, and the direction of effects is not discussed either, but potentially quite important. It seems that the choice bias captures how many effortful reward challenges are accepted overall which maybe captures general motivation or task engagement. Maybe it is then quite expected that this could be linked with questionnaires measuring general motivation/pleasure/task engagement. Formally, the choice bias is the constant term or intercept in the model for p(accept), but the authors never comment on what its sign means. If I'm not mistaken, people with higher anhedonia but also higher apathy are less likely to accept challenges and thus engage in the task (more negative choice bias). I could not find any discussion or even mention of what these results mean. This similarly pertains to the results on chronotype. In general, "choice bias" may not be the most intuitive term and the authors may want to consider renaming it. Also, given the sign of what the choice bias means could be flipped with a simple sign flip in the model equation (i.e., equating to accepting more vs accepting less offers), it would be helpful to show some basic plots to illustrate the identified differences (e.g., plotting the % accepted for people in the upper and lower tertile for the SHAPS score etc).

(3) None of the key effects relate to effort or reward sensitivity which is somewhat surprising given the previous literature and also means that it is hard to know if choice bias results would be equally found in tasks without any effort component. (The only analysis related to effort sensitivity is exploratory and in a subsample of N=56 per group looking at people meeting criteria for MDD vs matched controls.) Were stimuli constructed such that effort and reward sensitivity could be separated (i.e., are uncorrelated/orthogonal)? Maybe it would be worth looking at the % accepted in the largest or two largest effort value bins in an exploratory analysis. It seems the lowest and 2nd lowest effort level generally lead to accepting the challenge pretty much all the time, so including those effort levels might not be sensitive to individual difference analyses?

(4) The abstract and discussion seem overstated (implications for the school system and statements on circadian rhythms which were not measured here). They should be toned down to reflect conclusions supported by the data.